Sepsis, also known as systemic inflammatory response syndrome (SIRS) induced by infection, is a common complication of burn injury, trauma, tumor and infectious diseases, and now has been globally recognized as the leading cause of mortality in intensive care units (ICU). The existing principal clinical treatments of sepsis are initial antibiotic administration and remedy of hypoxic ischemic damage, which adopt conventional treatments of organ failure and shock, and there is no specific treatment for it up to now. Usually, medication to sepsis empirically adopts non-specific drugs, e.g. glucocorticoids, insulin, immunomodulator, etc., but their curative effect is still uncertain. In the 1990s, anti-lipid A monoclonal antibody HA-1A (Centoxin) was used in the treatment of sepsis after burn injury and trauma in the US Army during the Gulf War. Centoxin also was clinically used in some European country and Japan. However due to its possible adverse effect to septic shock, Centoxin failed to obtain approval by US Food and Drug Administration (FDA) in 1992 and then disappeared from the European market as well. Recombinant human activated protein C (rhAPC) is the only drug approved by FDA for sepsis treatment so far (tradename XIGRIS). Result of clinical trial shows that rhAPC, which obtain FDA marketing approval in November 2011, can reduce the 28-day mortality of patients suffering sepsis. However, result of the second clinical trial shows that there is no difference in 28-day mortality between the rhAPC group and the control group. In another clinical trial in 2007, rhAPC exhibits not only no effect in increasing the survival rate of patients suffering sepsis, but also the adverse effect of inducing severe bleeding tendency in patients. Therefore, the organizing institution of this clinical trial does not recommend rhAPC as clinical drug for sepsis treatment.
The discovery of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs) thereof have produced a qualitative upgrade on knowledge of sepsis. It has been proven that the pathogenesis of sepsis is that the PAMPs (including lipopolysaccharide/endotoxin (LPS), bacterial genomic DNA (CpG DNA), and peptideglycan (PGN)) of pathogens are recognized by corresponding PRRs in the membranes of or intracellular of inflammatory cells in non-specific immune system after the invasion of pathogens into organism, which process will cause inflammatory cells to be activated and release inflammatory mediators, resulting systemic inflammatory response and then organ damage. Because of the failure of existing treatments, e.g. antagonizing the important effector molecules in inflammatory response, correction of the disorders of coagulation and complement system, and antagonizing LPS alone, searching for drugs which could antagonize multiple major PAMPs (LPS, CpG DNA, PGN, etc.) concurrently and blocking the onset of sepsis at the source may bring a breakthrough on the sepsis treatment.
Kukoamine B is a naturally existing alkaloid isolating from Lycii cortex., one kind of traditional Chinese herbs, the chemical structure of which is as follows:

Kukoamine B, which exists in the form of free alkali, was first isolated from Lycii cortex. by Shinji Funayama of Japan in 1995 (S. Funayama, G. Zhang & S. Nozoe. Phytochemistry. 1995; 38: 1529-1531). There is no research about biological activity of kukoamine B reported, other than methods of extraction, isolation, purification and structural characterization thereof The use of kukoamine B in the preparation of drugs for the prevention and treatment of sepsis and autoimmune disease has been disclosed in the earlier Chinese patent application filed by applicant (Chinese patent application No. 201010156503.X).
The difference among kukoamine B contents in various Lycii cortex. from different habitats and picking time is comparatively large. Therefore, extraction, isolation and purification of kukoamine B from plants for the preparation of drugs for preventing and treating sepsis have such defects as instability in source, high production costs and high energy consumption. Chemical synthesis may provide a new method for the preparation of kukoamine B. However, no research on total chemical synthesis of kukoamine B was found so far after reviewing previous researches and patents.
As compared with naturally occurring kukoamine B, salts of kukoamine B exists in the form of salt and has a new chemical structure. The total chemical synthesis method of salts of kukoamine B has not been disclosed that the applicants are aware of by any patents and literatures so far. Until now, there is also no report that the applicants are aware of about the use of salts of kukoamine B in the treatment of sepsis, particularly through antagonizing multiple PAMPs (LPS and CpG DNA) concurrently.